The invention relates to a micromechanical pipetting device for pipetting liquid volumes in a range between a minimum value smaller than a microliter and a maximum value of about 10 microliters. The device comprises a pipetting module which has an inlet/outlet which may either be connected to a removable pipetting tip or may have a pipetting tip integrally built into the module. The integrally built pipetting module comprises a micromechanical structure which is integrally built on a silicon wafer.
Some micromechanical structures are known for the purpose of dispensing very small volumes of liquid. A micromechanical pump comprising valves can be used for this purpose, but high accuracy of the dispensed volumes cannot be attained, mainly due to the reflow caused by the operation of the valves and dead volumes and leaking problems associated with the use of valves. Moreover such micropumps normally pump a number of liquid portions until the desired volume to be dispensed is approximately attained. Thus the accuracy of the total volume dispensed depends from the accuracy of the volume portion transported by each pumping step.
A similar approach can also be implemented by dispensing microdrops, as in ink-jet printers, until the desired volume to be dispensed is approximately attained. Also in this case the accuracy of the total volume dispensed depends from the accuracy of the volume of each microdrop. The accuracy of pipetted volume obtained by this approach is limited, in particular because it depends on the properties of the liquid being pipetted.
Another known approach for dispensing very small volumes of liquid is the use of a micromechanical pump controlled by a feedback loop comprising an anemometric flow sensor and an integrator of the output signal of this sensor. The function of the feedback loop is to measure the volume pumped by the micromechanical pump and to control it accordingly. Thus in theory the feedback loop would control the micromechanical pump in such a way that the latter pumps a steady flow of liquid over an interval of time until the desired volume to be dispensed is attained and then the operation of the pump is stopped. This approach has several important disadvantages. There is always a delay between the measurement of the pumped volume and a corresponding control of the micromechanical pump. Thus a correction of the operation of the pump via feedback loop only happens after the pumped volume is already larger than the desired value. Such a device is therefore not accurate enough for pipetting very small volumes with high accuracy. The operation of anemometric flow sensors requires heating of the liquid pumped. Thus, such a device cannot be used for pumping thermally sensitive liquids of the kind to be pipetted e.g. in clinical chemistry analyzers.
The aim of the invention is therefore to provide a micromechanical pipetting device for pipetting with high accuracy very small volumes of liquids and with which the above-mentioned disadvantages of known prior art devices can be avoided.
According to the invention, this aim is attained with a device of the type described herein, which device is characterized in that it comprises.
a) a first chamber located within a pipetting module, wherein the volume contained within said first chamber may be modified by displacement of a membrane which is a portion of a wall of said chamber, said first chamber having only one opening, said opening being permanently open and allowing fluid flow into and from the interior of said first chamber,
b) a channel located within said pipetting module, said channel establishing a direct, valveless and permanent fluidical connection between said opening of the first chamber and the inlet/outlet of the pipetting module,
c) actuator means for displacing said membrane, and thereby aspirating or expelling a volume of air or of a liquid into or from said first chamber, which in turn causes aspiration or expulsion of a volume of a liquid sample through said pipetting tip, and
d) a first sensor means for generating a first output signal related to the displacement of the membrane.
The main advantage of the device according to the invention as compared with the prior art devices is that it makes it possible to pipette very small volumes of liquid with high accuracy, reproducibility, reliability and fast performance.
In particular the inclusion of a first sensor means for generating a first output signal related to the displacement of the membrane makes possible a highly accurate and real-time monitoring of the operation of the device which is suitable for the fast forward and reverse flow in a pipetting device according to the invention.
Moreover, the device according to the invention advantageously differs from prior art devices in that it makes it possible to pipette the entire volume to be pipetted by a single stroke of the actuator means.
A preferred embodiment of the device according to the invention further comprises a control means for controlling the operation of the actuator means in response to the first output signal generated by the first sensor means. The micropipetting module according to the invention and the means for controlling the operation of the actuator means are preferrably configured and dimensioned so that the total volume to be aspirated and dispensed with the pipetting tip is aspirated into the pipetting tip by means of a single stroke of the displacement movement of the membrane.
Another preferred embodiment of the device according to the invention is characterized in that a portion of the membrane is part of the first sensor means and the first output signal generated by this sensor means is related to or representative of the displacement of the membrane.
A further preferred embodiment of the device according to the invention is characterized in that a portion of the channel forms a second chamber and is part of a second sensor means for generating a second output signal representative of the pressure in the channel, and the means for controlling the operation of the actuator means is responsive to both the first and the second output signals.
A further preferred embodiment of the device according to the invention is characterized in that a portion of the channel forms a second chamber and is part of a second sensor means for generating a second output signal representative of the fluid flow through the channel, and the means for controlling the operation of the actuator means is responsive to both the first and the second output signals.
The above mentioned preferred embodiments which include the association of multifunctional sensors located close to the pipetting tip make possible a direct and highly accurate monitoring of very small pipetted volumes and early and active recognition and avoidance of malfunctions of the micropipetting module.
A further preferred embodiment of the device according to the invention is characterized in that a portion of the channel forms a third chamber which is located between the pipetting tip and the first or the second sensor means, said third chamber serving to prevent pipetted fluid from contacting the portion of the channel which comprises said first sensor means or said second sensor means.
A further preferred embodiment of the device according to the invention is characterized in that said actuator means comprises an electrostatic actuator or a piezoelectric actuator or an electromechanical actuator.
A further preferred embodiment of the device according to the invention is characterized in that said first sensor means is a capacitive or an electro-optical sensor.
A further preferred embodiment of the device according to the invention is characterized in that said second sensor means comprises a pressure or a flow measurement sensor. The use of an integrated pressure sensor according to the instant invention ensures that the pipetting module operates in the normal range (e.g. of viscosity) for which the system is designed.
A further preferred embodiment of the device according to the invention is characterized in that a plurality of said pipetting modules is integrally built on a silicon wafer.
A further preferred embodiment of the device according to the invention is characterized in that the pipetting tip is a silicon pipetting tip integrally built with the pipetting module.
Exemplified embodiments of the invention are described below with reference to the accompanying drawings.